近年来研究表明表观遗传学的改变在胃癌对化疗药物的耐受中起着重要作用。本课题组前期研究发现miR-34c启动子区CpG岛的高甲基化可能导致miR-34c的低表达，进而导致胃癌细胞对多种药物耐药。我们应用lncRNA芯片发现LINC00115在胃癌耐药细胞株中表达显著上调。应用RNAi技术在耐药株中封闭LINC00115，发现miR-34c启动子区甲基化水平下降，miR-34c表达上调。因此，我们提出假设LINC00115可能通过调节miR-34c的表达，最终影响胃癌细胞的耐药。该课题从细胞、组织标本和动物实验三个层面,通过lncRNA表达水平检测，DNA甲基化检测，RNA共沉淀，免疫共沉淀，染色质免疫共沉淀联合测序，慢病毒转染荷瘤鼠等方法系统研究并阐明LINC00115与 miR-34c之间的关系，以及在胃癌细胞耐药形成中的作用，为开展通过表观遗传学调控逆转胃癌耐药的研究提供重要理论依据。

o Recently, more and more researchs show that epigenetic plays an important role in resistance to chemotherapy in gastric cancer. Our research found that miR-34c was associated with drug-resistant in gastric cancer. Hypermethylation of CpG islands neighboring the miR-34c promoter reduced expression of miR-34c, which in turn reduced the chemosensitivity of gastric cancer. In addition, we found LINC00115 rose up significantly in MDR gastric cancer cell line using lncRNA chip. When LINC00115 was interfered using RNAi, the methylation of the miR-34c promoter was reduced, associating with increased expression of miR-34c in gastric cancer cell lines. Therefore, we assume that LINC00115 may regulate the expression of miR-34c, and eventually affects the resistance of gastric cancer cell. The study will carry out from three aspects the cells, tissues and animal experiments. Through the detection of the expression levels of lncRNA, the analysis of DNA methylation, RNA immunoprecipitation , Co-immunoprecipitation, Chromatin immunoprecipitation-Sequencing, we will clarify the relationship between LINC00115 and miR-34c, and the role of LINC00115 in the formation of resistance of gastric cancer. This will provide important theoretical basis for reversing drug resistance of gastric cancer by regulation of epigenetic.